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Browsing by Author "Burney, Heather N."
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Item A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study(Frontiers Media, 2021-09-17) Mamdani, Hirva; Schneider, Bryan; Perkins, Susan M.; Burney, Heather N.; Kasi, Pashtoon Murtaza; Abushahin, Laith I.; Birdas, Thomas; Kesler, Kenneth; Watkins, Tracy M.; Badve, Sunil S.; Radovich, Milan; Jalal, Shadia I.; Surgery, School of MedicineBackground: Most patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients. Methods: We conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population. Results: Thirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56-84%) with median RFS of 21 months (95% CI, 14-40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05-0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15-0.93, p = 0.0351, respectively). Conclusions: Adjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.Item Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes(Old City Publishing, 2022) Mereniuk, Todd R.; Burney, Heather N.; Lautenschlaeger, Tim; Watson, Gordon A.; Rhome, Ryan M.; Radiation Oncology, School of MedicinePurpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.Item FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease(Wolters Kluwer, 2022-07-05) Halim, Arvin; Burney, Heather N.; Li, Xiaochun; Li, Yang; Tomkins, Claudia; Siedlecki, Andrew M.; Lu, Tzong-shi; Kalim, Sahir; Thadhani, Ravi; Moe, Sharon; Ting, Stephen M.S.; Zehnder, Daniel; Hiemstra, Thomas F.; Lim, Kenneth; Medicine, School of MedicineBackground: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO2Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO2Max by kidney transplantation. Methods: We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment. Results: Patients across FGF23 quartiles differed in BMI (P=0.004) and mean arterial pressure (P<0.001) but did not significantly differ in sex (P=0.5) or age (P=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO2Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P<0.001), greater left ventricular mass index (LVMI; P<0.001), reduced HR at peak exercise (P<0.001), and maximal workload (P<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (P<0.001) before improvement in VO2Max at 1 year (P=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO2Max in advanced CKD (P<0.001) and after improvement after kidney transplantation (P=0.006). FGF23 was associated with LVMI before kidney transplantation (P=0.003), however this association was lost after adjustment for dialysis status (P=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models. Conclusions: FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.Item Incidence of Dementia and Alzheimer Disease Over Time: A Meta-Analysis(Wiley, 2019-06-20) Gao, Sujuan; Burney, Heather N.; Callahan, Chris M.; Purnell, Christianna E.; Hendrie, Hugh C.; Biostatistics, School of Public HealthBackground/Objectives: Population-based incidence estimates of dementia and Alzheimer’s disease (AD) provide important information for public health policy and resource allocation. We conducted a meta-analysis of published studies that reported age-specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time. Design: PubMed and MEDLINE were searched for publications through June 30, 2017 using keywords dementia, Alzheimer, and incidence. Inclusion criteria for the meta-analysis are: (1) population-based studies using personal interviews and direct examinations of the study subjects, (2) Standardized clinical diagnosis criteria, (3) Reporting age-specific incidence rates, (4) Published in English, and (5) Sample size greater or equal to 500 and length of follow-up greater or equal than two years. Mixed effects models were used to determine the association between birth year and incidence rates. Measurements: Age-specific dementia/AD incidence rates and their standard errors reported in each study. Results: Thirty-eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65-74, 75-84 and 85+). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups while studies in non-Western countries showed significantly increased AD incidence rates for the 65-74 age group (OR=2.78, p=0.04), but non-significant association for the 75-84 or 85+ groups. Conclusion: Dementia incidence declined over the last four decades, but AD incidence did not decline. Further research, especially from non-Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.Item Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity.(AHA, 2022-07-19) Arroyo, Eliott; Umukoro, Peter E.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Lane, Kathleen A.; Sher, S. Jawad; Lu, Tzong-Shi; Moe, Sharon M.; Moorthi, Ranjani; Coggan, Andrew R.; McGregor, Gordon; Hiemstra, Thomas F.; Zehnder, Daniel; Lim, Kenneth; Kinesiology, School of Health and Human SciencesBackground The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross-sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low-frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min·1.73 m), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min·kg) compared with predialysis (22.7 [5.2] mL·min·kg; <0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index (<0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage >12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min·kg) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min·kg; =0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low-risk New York Heart Association class I and higher-risk New York Heart Association class II to IV heart failure.Item Nondirected Living Kidney Donation and Recipient Outcomes in the United States: A 20-Year Review(Elsevier, 2022-03-22) Jan, Muhammad Y.; Yaqub, Muhammad S.; Adebiyi, Oluwafisayo O.; Taber, Tim E.; Anderson, Melissa D.; Mishler, Dennis P.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Sharfuddin, Asif A.; Medicine, School of MedicineIntroduction: Nondirected donation (NDD) of the kidneys is a growing practice where donors who do not have any genetic or emotional relationship are selected to donate to a wide variety of recipients with a range of selection criteria and decisions which are left up to individual transplant centers. Methods: We review all adult living kidney donor-recipient (DR) pairs and outcomes from NDDs who were recorded in United Network for Organ Sharing (UNOS) database as code 10 (anonymous) from October 1997 to September 2017 for demographics and outcomes. Results: A total of 2174 DR pairs were identified. The number of NDDs increased from 18 in 2000 to 256 in 2016. Survival analysis showed higher death-censored-graft survival (DC-GS) when recipient was 20 years or more older than donor followed by recipient-donor within 20 years of age and lowest when donor was 20 years or more older than recipient (P = 0.0114). Conclusion: Overall, the number of NDDs has increased significantly in the 20-year review period. Transplants from NDDs have excellent long-term outcomes. Better matching of controllable DR factors, such as age and body mass index (BMI), could further improve GS. Further research is needed to incorporate these DR factors into paired kidney donation programs potentially enhancing the utility and beneficence of this invaluable donation.Item Relationship between klotho and physical function in healthy aging(Springer, 2023-11-30) Arroyo, Eliott; Leber, Cecilia A.; Burney, Heather N.; Narayanan, Gayatri; Moorthi, Ranjani; Avin, Keith G.; Warden , Stuart J.; Moe, Sharon M.; Lim, Kenneth; Medicine, School of MedicineEpidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.Item A Retrospective Analysis of 287 Patients Undergoing Prophylactic Radiation Therapy for the Prevention of Heterotopic Ossification(Elsevier, 2020-11-24) Freije, Samantha L.; Kushdilian, Michael V.; Burney, Heather N.; Zang, Yong; Saito, Naoyuki G.; Radiation Oncology, School of MedicinePurpose: Heterotopic ossification (HO) is a potentially disabling disorder of ectopic bone formation secondary to orthopedic surgery or trauma. In this retrospective analysis we evaluated the outcomes of patients who received radiation therapy (RT) for HO prophylaxis. Methods and materials: A total of 287 patients who received RT for HO prophylaxis at a major trauma center from 2007 to 2018 were analyzed. Data collected included types of injury, surgery, time intervals between key events, development of postprophylaxis HO, and secondary malignancies. Associations between various factors and the risk of developing HO were analyzed. Kaplan-Meier analysis was used to estimate failure rates. Results: The most common indication for RT was traumatic acetabular fracture (83.3%). Twelve patients (4.2%) developed postprophylaxis HO with a median time to failure of 8.6 months (2.8-24.5). Kaplan-Meier 1-, 2-, and 5-year failure rates were 3.7%, 4.4%, and 7.4%, respectively. Injury type and timing of RT were not associated with the risk of failure, but we observed a trend of increased risk of failure in patients with longer time between surgery and RT (odd ration [OR] 1.68, P = .056). Current or former smokers (51.7%) were less likely to fail (OR 0.10, P = .03). There was no incidence of in-field secondary malignancy. Conclusions: There was no significant association between injury and fracture type, surgical approach, or timing of RT and development of HO, contrary to published reports of increased HO risk with certain surgical approaches and longer time intervals between injury and surgery, suggesting that prophylactic RT might play a role in mitigating these effects. Decreased risk of postprophylaxis HO among former or current smokers was unexpected. No secondary malignancy in the RT field was identified, although the median follow-up was only 17 months. Compared with published HO incidences (17%-39%) in patients who receive no prophylaxis after traumatic acetabular fractures, our results are highly suggestive of the efficacy of prophylactic RT.Item Testing Influences of APOE and BDNF Genes and Heart Failure on Cognitive Function(AAHFN, 2020) Jung, Miyeon; Apostolova, Liana G.; Gao, Sujuan; Burney, Heather N.; Lai, Dongbing; Foroud, Tatiana; Saykin, Andrew J.; Pressler, Susan J.; School of NursingBackground Apolipoprotein E ( APOE) ε2, ε4 and brain-derived neurotrophic factor ( BDNF) Val66Met alleles have been associated with cognition. Associations of these alleles with cognition in heart failure (HF) and influences of HF across the cognitive spectrum (i.e., cognitively normal to Alzheimer's dementia [AD]) remain unexplored. Objectives To investigate influences of APOE ε2, ε4, BDNF Met and HF on cognition among participants across the cognitive spectrum. Methods Genetic association study using national databases ( N = 7,166). Results APOE ε2 frequencies were similar across the cognitive spectrum among participants with HF. APOE ε4 frequency was lower among participants with HF and AD than non-HF participants with AD. BDNF Met frequencies did not differ across the spectrum. HF was associated with worse attention and language. In the HF subsample, ε4 was associated with worse memory. Conclusion Associations between APOE and cognition may differ in HF but need to be tested in a larger sample.Item Vasopressin for Post-kidney Transplant Hypotension(Elsevier, 2022-04-07) Jan, Muhammad Y.; Moe, Sharon M.; Adebiyi, Oluwafisayo; Chen, Jeannie; Powelson, John; Burney, Heather N.; Yaqub, Muhammad S.; Mishler, Dennis P.; Moorthi, Ranjani N.; Taber, Tim E.; Anderson, Melissa D.; Li, Yang; Li, Xiaochun; Fridell, Jonathan A.; Goggins, William C.; Sharfuddin, Asif A.; Medicine, School of MedicineIntroduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.